1. Introduction of Cohort Study
Aug, 17, 2011
Introduction of Cohort Study
Nice see you again and nice to meet you for somebody.
It is my great pleasure to make lecture today.
In my part, I would like to talk about cohort study briefly.
Hirohide Yokokawa, M.D., Ph.D.
Department of General Medicine,
Juntendo University School of Medicine

2. Contents What is Cohort Study? Overview of study design
Purpose of Cohort study
Types of Cohort Studies
Prospective and Retrospective
Procedure of Cohort Study.
Follow up and Risk assessment
An Example of Cohort Study.
Contents of my lecture. At first, I introduce outline of Cohort study and major types of the study. And then, I explain procedure, follow up and risk assessment, and finally introduce my study as an example.

3. Overview of study designs
Clinical studies
This slide shows overview of major study design.
You can see here that, Clinical studies are listed top of six, and cohort study is relatively high ranked.
However, the ranking is not always absolute. In some case, well designed case-control study may have better potential compared to cohort study. Therefore, select the study design carefully considering with study question and feasibility.

4. In belief, the Cohort study examines factors associated with developing sickness in time passes.

5. Purpose of Cohort Study
To determine whether there is an association between a factor and development of a disease. To derive an appropriate interference regarding with a possible causal relationship.
I summarize the main purpose of Cohort study in the study.
First is to determine whether there is an association between a factor and development of a disease.
Second is to derive an appropriate interference regarding with a possible causal relationship.

6. Advantage and Disadvantage of Cohort Study compared to Case-Control study
Measures
Incidence Rate, Relative Risk(RR)
Odds Ratio (OR) only
Cost
Expensive
Inexpensive
Study term
Long term
Short term
Sample size
Need large sample
Powerful with small sample cases
Exposure
Good for rare exposure
Limited to rare exposure
Disease
Poor potential for rare
Possible for several disease
Good for rare disease
Only one disease
Causal
Potentially strong
Potentially less strong
Generalization
Possibly generalizable
Probably not generalizable
Please remember Dr.Koriyama’s lecture. Cohort study has several advantage. Meanwhile there are several difficulties to carry out the study.

7. Review feasibility of the planed study considering with study question, target disease, expose, cost, expected study period , etc!
So I strongly recommend you review feasibility of the planned study considering with target disease, expose, cost, expected study period.

8. Define Study Participants
Procedure of Cohort Study ①
Define Study Participants
EXPOSED
NOT
EXPOSED ② ③ ④
Basic procedure of cohort study is shown here.
At first, we have to define the eligible study participants prior to starting the study.
Next, EXPOSED as Cases, and NOTT EXPOSED as Controls are estimated.
After follow up, we measure target outcome accurately and compare incidence of the outcome.
DISEASE
DEVEPOPS
DISEASE
DOSE NOT
DEVEPOPS
DISEASE
DEVEPOPS
DISEASE
DOSE NOT
DEVEPOPS

9. Define eligible Study Participants
The investigator selects a group of EXPOSED individuals and a group of NON EXPOSED individuals
Follow up both groups
Compare incidence of disease

10. Follow up
To obtain data about outcome to be determined (morbidity or death)
Mailed questionnaire, telephone calls
Periodic medical examination
Reviewing records
Surveillance of death records
Follow up is the most critical part of the study
Some loss to follow up is inevitable due to death change of address, migration, change of occupation.
Loss to follow-up is one of the draw-back of the cohort study.
Follow up is one of the most important steps. We must obtain accurate data about outcome from these sources.
However, some loss to follow up is inevitable due to these reasons. Thus, loss to follow up is one of the draw-back of the cohort study and we have to do our best to minimize loss to follow up.

11. Types of Cohort studies
Prospective
Retrospective
There are several types in Cohort study.
Today, I would like to talk about prospective and retrospective.

12. Time course of Cohort studies
NOW
EXPOSE
OUTCOME
Collect Information
Measure
Outcome
In both types, flow of time is same like that outcome is measured after EXPOSE. Time of outcome measurement is different.
First one is that EXPOSE was in past and outcome is measured in present.
On the other hand, another one is that EXPOSE is estimated in present and outcome will be measured in future.
EXPOSE
OUTCOME
Time

13. Retrospective Cohort Study
(10 years follow-up)
2001
(10 years ago)
Study Participants
EXPOSED
NOT
DISEASE
DEVEPOPS
DOSE NOT
First one is retrospective study. In this study, we measure outcome in present and collect expose information retrospectively using past record and estimate past EPOSED status.
2011 (Now)

14. Prospective Cohort Study
(10 years follow-up)
2011
Now
Study Participants
EXPOSED
NOT
DISEASE
DEVEPOPS
DOSE NOT
Another one is prospective Cohort study.
We estimate present EXPOSED status, and will measure outcome in future after follow up.
2021

15. Advantage and Disadvantage of
Prospective and Retrospective Cohort Study
Prospective
Retrospective
Cost
Expensive
Inexpensive
Needed time for study
Long term
Short term
(Possible to determine measure factors and outcome at same time)
Validity for exposed information
Good validity
Relatively less validity
Adding new measures
Possible
Impossible
Please make sure advantage and disadvantage of these studies.
Prospective study is good validity and possible to add new measures, but expense and needed long time follow up.
Please review your study again considering these advantage and disadvantage.

16. Risk measurement in Cohort Study
DISEASE
NOT
PRESENT
DISEASE
PRESENT
EXPOSED a b
Follow-up c d
NOT EXPOSED
We can make a risk assessment in Cohort study calculating Relative Risk.
The risk can be defined as probability of developing a disease in EXPOSED compared to NOT EXPOSED.
Risk in EXPOSED
Risk in NOT EXPOSED
a/(a+d)
c/(c+d)
Relative Risk (RR)= =

17. Interpretation of Relative Risk (RR)=1
No association
>1
Risk in EXPOSED greater than Risk in NOT EXPOSED
(Positive association; Risk Factor)
<1
Risk in EXPOSED less than Risk in NOT EXPOSED
(Negative association;
Protective Factor)
If RR is equal to 1, it means no association between EXPOSED and NOT EXPOSED.
If RR is greater than 1, EXPOSE is risk factor.
If RR is less than 1, EXPOSE is protective factor, like as Vaccine.

18. An Example of Cohort Study and A Case of Publishing Data
Finally, I would like to introduce briefly my study as an example.

19. Gaps between hypertension treatment guidelines and practice in Japan
Fukushima Research of Hypertension
～(FRESH)～
I have conducted a Cohort study and the title is Gaps between hypertension treatment guidelines and practice in Japan
The study team name is Fukushima Research of Hypertension.
Hirohide Yokokawa，Aya Goto，Hironobu Sanada，
Tsuyoshi Watanabe，Robin A. Felder, Pedro A. Jose,
Seiji Yasumura

20. Introduction of our Cohort study
Fukushima Research of Hypertension (FRESH)
Research Design
Observational Cohort Study
(from July 2006 to May 2007)
Subjects
The study is observational Cohort study and 3358 patients with HYPERTENSION were registered by 72 physicians.
Subjects were 3,358 registered hypertensive patients who received antihypertensive medication by 72 physician members of Fukushima Hypertension Conference.

21. Aim of the study Fukushima prefecture To determine
Hypertensive patients’ characteristics
Success rates in achieving goal blood pressures
Factors associated with therapeutic failures for target treatment goals among Japanese hypertensive patients.
Main aim of the study is to determine
Hypertensive patients’ characteristics
Success rates in achieving goal blood pressures
Factors associated with therapeutic failures for target treatment goals among Japanese hypertensive pa
Fukushima prefecture

22. Return these forms by mail
Time Course of the Study
Summer
Autumn
Winter
Spring 夏
2006-July
Registration
2006-October
1st Follow-up
2007-Janualy
2st Follow-up
2007-April
3st Follow-up
Fulfill Registration form and collect basic information
Fulfill Follow-up form and collect follow-up data
The study is composed with baseline survey and three follow-up surveys.
Return these forms by mail 22

23. Gaps between hypertension treatment guidelines and practice in Japan
Analysis of Baseline Data
(Cross-sectional analysis)
Gaps between hypertension treatment guidelines and practice in Japan
～Baseline survey results from Fukushima Research of Hypertension (FRESH)～
Baseline data is already published in Journal of Clinical Hypertension, which is an official Journal of American Society of Hypertension.
J Clin Hypetens 2009; 11:

24. To assess the possible factors associated with the focused outcomes using baseline data.
The aim of baseline data analysis is to assess the possible factors associated with focused outcomes.

25. Table.1 Association of blood pressure achievement failure in elderly patients without DMa) or RDb) (multivariate logistic regression analyses)
Variables
Odds Ratio
95% Confidence Interval
Waist circumference (cm)c)
1.26 *
Number of antihypertensive drug used 1
1.00(Reference) 2
1.15 3
1.96
Among elderly patients with the diseases, obesity and number of antihypertensive drugs were risk factors for achievement failure.
*<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease
c) 85 or higher for Men, 90 or higher for Women

26. *<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease
Table.2 Association of blood pressure achievement failure in young and middle aged patients without DMa) or RDb) (multivariate logistic regression analyses)
Variables
Odds Ratio
95% Confidence Interval
Body mass index (BMI) 25 or higher
1.74 *
Family history of hypertension (yes)
1.67
Organ damage/ cardiovascular disease
Brain (yes)
0.33
Hypertensive retinopathy (yes)
Among young and middle aged patients with DM or renal disease, obesity and family history hypertension were risk factors for achievement failure. However, cardiovascular complications were protective factor.
*<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease

27. *<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease
Table.3 Association of blood pressure achievement failure in patients with DMa) or RDb) (multivariate logistic regression analyses)
Variables
Odds Ratio
95% Confidence Interval
Body mass index (BMI) 25 or higher
1.34 *
Family history of diabetes mellitus
(yes)
1.40
Dyslipidemia (yes)
1.41
Organ damage/ cardiovascular disease
Brain (yes)
0.62
Blood vessel (yes)
0.48
Among patients with the disease, obesity family history DM and dyslipidemia were risk factors. However, cardiovascular complications were also protective factors.
The result is seemed to be contradicting. In the last of my lecture, let’s discuss with me.
*<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease

28. Caution!
It is limited to interpret causal relationship in cross-sectional data.
Need longitudinal data analysis to access causal relationship.
As you know, it is limited to interpret causal relationship in cross-sectional data. Therefore, it is needed longitudinal data analysis to access causal relationship.

29. Analysis of Follow-up Data (Longitudinal analysis)
Longitudinal community-based assessment of blood pressure control among Japanese hypertensive patients: Fukushima Research of Hypertension (FRESH)
Longitudinal analysis was already published in the journal.
J Clin Hypetens 2010;12:166–173.

30. Flow of registered patients
3358 registered initially
3320 followed through a year
38 excluded due to missing data
or lack of medication use
2735 continued
and
confirmed their medical information
585 excluded
due to lost follow up or missing data
1318 Elderly Patients
without
DMa) or RDb)
480 Young or Middle
aged Patients
937 DMa) and RDb)
Follow-up rate
82.6%
After one year follow up, 585 were lost. Thus, follow-up rate was 82.6%.
a)DM; Diabetes mellitus, b)RD; Renal disease.

31. Table 1. Proportions of year-round failure and success in
achieving blood pressure goals.
N (%)
Groups
Year-round failure
Year-round success
Elderly patients without
DMa) or RDb) (n=1319)
124 (9.4)
407 (30.8)
Young or middle aged patients
without DMa) or RDb) (n=482)
207 (42.9)
19 (3.9)
Patients with DMa) or RDb)
(n=942)
429 (45.5)
39 (4.1)
We estimated rates of year-round failure and success.
You can see here that, among young or middle aged patients without DM or renal disease, or patients with the diseases, year-round success rates were extremely low. In other words, these patients were uncontrolled through a year.
a)DM; Diabetes mellitus, b)RD; Renal disease

32. Table 3-1. Risk factors for failure to meet blood pressure
goals in elderly patients without DMa) or RDb)
across all seasons.
(multivariate logistic regression analysis) 　　
Significant variables
N (%)
Odds Ratio
95% Confidence Interval
Number of antihypertensive
drug used 1
632 (47.9)
1.00 2
508 (38.5)
2.08 ** 3
180 (13.6)
4.45
Presence of organ damage or
cardiovascular disease
475 (36.0)
0.55
Among elderly patients the disease, number of antihypertensive drugs was also risk factor. However, cardiovascular complications was protective factor.
a)DM; Diabetes mellitus, b)RD; Renal disease
**<0.01

33. Table 3-2. Risk factors for failure to achieve blood
pressure goals in young or middle aged patients
without DMa) or RDb) across all seasons.
(multivariate logistic regression analysis)
Significant variables
N (%)
Odds Ratio
95% Confidence Interval
Gender (male)
274 (56.8)
0.63 **
Body mass index (≥25)
204 (42.6)
2.11
Presence of organ damage
or cardiovascular disease
88 (18.3)
0.47
Among young or middle aged patients without the disease, male sex, obesity were risk factors.
Like as baseline data, cardiovascular complications was protective factor.
a)DM; Diabetes mellitus, b)RD; Renal disease
**<0.01

34. Table 3-3. Risk factors for failure to achieve blood
pressure goals in patients with DMa) or RDb)
across all seasons.
(multivariate logistic regression analysis)
Significant variables
N (%)
Odds Ratio
95% Confidence Interval
Family history
Hypertension (yes)
508 (53.9)
1.40 **
Alcohol consumption (daily)
175 (18.7)
1.64
Current smoking status
128 (13.6)
1.53
Instruction in home blood pressure
measurement (yes)
560 (59.6)
1.41
Dyslipidemia (yes)
511 (54.4)
1.35
Presence of organ damage or
cardiovascular disease
459 (48.8)
0.58
Among patients with the disease, family history of hypertension, alcohol consumption, current smoking, instruction in home blood pressure measurement and dyslipidemia were risk factors. However, cardiovascular complications were also protective factor.
a)DM; Diabetes mellitus, b)RD; Renal disease

35. The Odds Ratio in Cohort Study
Year Round Failure
NOT Year Round Failure
Atherosclerotic Complications a b
Not Atherosclerotic Complications c d
Odds in Atherosclerosis complications
Odds in NOT Atherosclerosis Complications
I already talk about Relative Risk.
However, in my case, I calculate Odds Ratio. Because, I evaluated year round failure not incidence. Therefore, I calculated Odds Ratio.
a/b
c/d
Odds Ratio (OR)= =